Project summary Early vaginal wall detachment often results in pelvic organ prolapse (POP). POP is a common disease in the aging woman with a high morbidity rate related to treatment. Approximately 30-40% of women may experience this condition, and by 80 years-old about 20% or so will need to undergo corrective surgery. However, current synthetic materials for corrective surgery have been popular but can lead to severe complications as recognized by the FDA in two notifications (2008, 2011) along with a high prolapse recurrence rate. Furthermore, the POP treatment is delayed until advanced stages due to late recognition and variable symptomatology. To reduce POP morbidity and treatment cost, a strategy to address early vaginal wall detachment to prevent POP development would be highly desirable. Such a preventive treatment could employ an appropriate biodegradable bio-adhesive material to reattach the detached vaginal wall to the pelvic muscle in order to prevent further drop and detachment of the anterior vaginal wall and vaginal apex resulting in POP. Our preliminary work indicates that a biodegradable mussel-inspired adhesive is a good candidate to attain this preventive goal, but it needs further improvement in adhesive strength properties and tissue durability. In this project, our goal is to develop a novel adhesive material from mussel-inspired adhesive and biodegradable nanoparticles specific for early vaginal wall detachment. To realize this goal, three specific aims are proposed. In Aim 1, we will prepare and optimize our current biodegradable nanoblend adhesive by altering its chemical structure, component concentrations, nanoparticle contents and surface. In Aim 2, we will evaluate the adhesive strength of the nanoblend using an ex vivo tissue model and assess the material biosafety, adhesive strength and tissue growth in vivo using a rat model. In Aim 3, we will incorporate a cell recruiting chemokine into the adhesive, which can recruit stem cells to promote new tissue formation to permanently enhance the attachment between pelvic floor and muscle. We will further determine the efficacy of this bioactive adhesive using a rat model. Three innovative aspects are proposed. The first is the novel concept of prevention strategy to manage early vaginal wall detachment to reduce the morbidity of POP, which can improve the life quality of the women patients and save therapy costs. The second is the implementation of a novel biodegradable adhesive material system. It will provide rapid and robust adhesive to reinforce the detached vaginal wall from the pelvic muscle, and allow new tissue ingrowth. The nanoparticles can increase the adhesive strength and also served as carriers to deliver biofunctional molecules. The third is that this nanoblend adhesive can also works for cell recruitment and tissue regeneration. The successful outcome of this project will provide a novel strategy to treat patients with early vaginal wall detachment to prevent POP occurrence, thus resulting in reduced morbidity and associated treatment cost. The developed materials and methodologies could be used for other biomedical applications such as tissue glue and wound healing.